Zinc is undoubtedly one of the most important forms of currency your body needs to pay its bills, especially for IBS, immunity and depression.
It’s hard to simplify just how many of these transactions it pays for in a day, but maybe some fun facts might better illustrate it.
Of all the trace elements in the body, only iron is more abundant than zinc.
Remember, iron is a significant part of your red cells, so if you take that function away, then zinc becomes the most abundant metal-based element in your body![i]
You walk around with around 2-3gms of zinc in your body every day.[ii] It’s in all tissues in the body, with eighty-five per cent of body zinc found in your muscles and bones and eleven per cent seen in your skin and liver.[iii]
Estimates suggest that 2 billion people are zinc deficient globally, with other estimates suggesting that up to fifty per cent is at risk.[iv] But this is not the case in developed places such as Hong Kong, where over-supplementation can interfere with iron and copper levels and diminish HDL cholesterol levels, even at low doses.[v]
This potential for regional differences in zinc consumption precisely illustrates the contrast between using a supplement to replace dietary insufficiencies, using a supplement for a therapeutic outcome and testing levels in individuals instead of assuming everyone is deficient.
At-risk populations, aside from developing countries, are the elderly, with nearly thirty per cent of the population considered deficient[vi], vegans and vegetarians, and people who live with chronic diseases and chronic diarrhoea.[vii]
In this article, we’ll be a little more specific. Focusing on why zinc may be essential if you are struggling with your IBS, immune system, and depression.
Zinc is critical for the function of the immune system, and that’s an understatement.
I’ve often said to patients that the best way to think about zinc is essential for all fast-dividing cells, and its function within the immune system is a perfect example.
Zinc has been referred to as the “gatekeeper of the immune system”[viii], and I think that’s perfect.
Primarily, we understand the connection between zinc and the immune system through research into a deficiency’s effects on the body.
Deficiencies in zinc affect the innate immune system, which initiates immediate responses to viruses and other pathogens. The adaptive immune system comprises T and B cells that are more surgical when it comes to their targets.[ix]
Zinc deficiency can also drive T-helper cells to become imbalanced, an origin story for many allergy-based symptoms. In contrast, supplementation of zinc or correction of deficiency can reverse this imbalance dampening the inflammatory cells that cause autoimmunity.[x]
Correction of deficiency has also been studied related to illnesses such as acute lower respiratory infections in children.
One study, in particular, found that zinc supplementation may reduce death in children suffering from these infections in populations with poor levels of zinc in their diet.[xi]
Higher standard meta-analysis studies have also seen oral zinc supplementation reduce the duration of cold symptoms. A study from 2021 showed better symptom scores after three days and higher prevention rates of respiratory tract infections in adult populations unlikely to be deficient.[xii] This conclusion also suggests that supplementation with zinc can be helpful aside from mitigating the effects of a deficiency.
In our new world, zinc has also generated some interest regarding its potential role in SARS-Co V-2.
At the time of writing this at the beginning of 2022, there is indirect evidence suggesting there may be reductions in risk, duration and severity.[xiii]
A retrospective study in Spain with hospital admitted patients showed those who passed away had significantly lower zinc levels than the patients who survived.[xiv]
A study in Japan also had similar results.[xv] Still, both studies had small numbers and did not discuss the mechanism of how zinc was implicated aside from the presence of its deficiency.
An important point is there is an equal chance that if zinc deficiency was present, then other deficits critical in the immune response may also have been current, compounding the problem.
The first randomised controlled trial pairing zinc with high dose vitamin C showed no benefit for ambulatory patients[xvi] , so we’ve got to watch this space and see how that goes.
Zinc is a pillar of a successful digestive treatment for IBS-D.
Zinc’s role in wound healing, significant for the skin, which we won’t discuss in this article, has been studied as a longer-term solution for IBS brought on by leaky gut.[xvii] Zinc does this by bringing the tight junctions of the gastrointestinal tract back together, the same tight junctions that are inflamed and leaky in the first place.
It’s also thought to have a crucial role in balancing out the environment of the small intestine.[xviii]
Let’s look at zinc deficiency symptoms first, as we did with the immune system. Zinc deficiency in its more severe form has been linked as an origin story for some cases of diarrhoea.[xix]
Furthermore, post this discovery, it was then found that chronic diarrhoea conditions such as IBS-D can cause a zinc deficiency, thus creating a perpetuating cycle.[xx] The connection has evolved so far that zinc supplementation in developing countries has decreased diarrhoea prevalence, morbidity, and mortality.[xxi]
The most prescribed medicine globally, Proton Pump inhibitors can cause a zinc deficiency.
Staying with the theme of deficiency, another major contributing factor to the development of zinc deficiency is proton pump inhibitor drugs or PPIs. Some studies have found that just eight weeks of using omeprazole can lower serum scores due to the action of PPIs diluting the acidity of the gastric juice.[xxii]
Functionally, zinc is also a necessary form of currency when it comes to the production of gastric juice,[xxiii]making it essential when it comes to repairing the gut and helping you digest your food properly.
Now, we are yet to get into zinc’s role in illnesses such as chronic fatigue syndrome and inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease. I hope as an introduction, you are building a theme of just how vital a form of currency zinc is for the gut and the brain. Speaking of which, let’s look at zinc’s function within the brain.
Zinc has clear evidence around its role in depression.
When it comes to depression and its treatment in the clinic, zinc is the first or second consideration. Our focus has been on zinc in the broader community and its function in the immune system. Did you know that imbalances in zinc levels in the brain cause changes in behaviour, learning, mental function, and susceptibility to epileptic convulsions?[xxiv]
Further to this, studies have confirmed that serum zinc levels are lower in depressed patients when compared to normal controls.[xxv]
Zinc is also heavily concentrated in the limbic system, commonly referred to as the brain’s emotional centre.[xxvi] It’s no wonder that it, along with magnesium, has been nominated as one of the primary nutrients to augment anti-depressant therapy. Especially in treatment-resistant depression.[xxvii] An extension of this is a yet unproven hypothesis that zinc supplementation may reduce the amount of psychotropic medication required over the long term. This reduction leads to more favourable outcomes and a more straightforward treatment over time.[xxviii]
Note: This is not a reason to discontinue or change your medication, just some positive direction for the future. If you are curious, chat with your healthcare practitioner about creating a plan involving zinc as an accompaniment to your current protocol.
There are a few potential reasons we think zinc helps so many people in depression.
The first is zinc’s ability to increase brain-derived neurotrophic factor, commonly known as BDNF. A molecule that helps look after your neurons and your brain’s plasticity. We now have numerous studies that BDNF is decreased in people living with depression,[xxix] and supplementation of zinc goes some way to correcting this.[xxx]
As a side note to the BDNF conversation. One of the other things that increase BDNF and positively affects depression is, wait for it, exercise![xxxi]
Another potential mechanism is a complicated one, but to make it easier. Let’s say that receptors in the brain that help it be less excited are heavily reliant on zinc. These receptors are called NMDA receptors.
If the brain doesn’t have enough zinc to pay the transactions required for these receptors to do their jobs, the brain stays overexcited and makes you feel wired, anxious, depressed and tired.
I’m going to write a whole article on how this NMDA system affects your mental health. So rest assured that I’ll do my best to help you understand how important this can be for your mental health and how you can test it in the future.
So you’ve gotten this far, now what?
Get your zinc tested. Ask your healthcare practitioner to test your serum zinc levels and see where you are on the scale. Correcting your zinc levels can be beneficial for IBS, immunity and depression. As I hope I have shown here. However, I want to reiterate that taking zinc when you don’t need it can be deleterious for you and may have you getting worse, so best start with a baseline you can work with and retest from there.
Hope this helps, Philip.
[i] Jurowski, K., Szewczyk, B., Nowak, G. et al. Biological consequences of zinc deficiency in the pathomechanisms of selected diseases. J Biol Inorg Chem 19, 1069–1079 (2014). https://doi.org/10.1007/s00775-014-1139-0
[ii] Maret W, Sandstead HH. Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol. 2006;20(1):3-18. doi:10.1016/j.jtemb.2006.01.006
[iii] Calesnick B, Dinan AM. Zinc deficiency and zinc toxicity. Am Fam Physician. 1988;37(4):267-270.
[iv] Golub MS, Keen CL, Gershwin ME, Hendrickx AG. Developmental zinc deficiency and behavior. J Nutr. 1995;125(8 Suppl):2263S-2271S. doi:10.1093/jn/125.suppl_8.2263S
[v] Fosmire GJ. Zinc toxicity. Am J Clin Nutr. 1990;51(2):225-227. doi:10.1093/ajcn/51.2.225
[vi] Wessels I, Maywald M, Rink L. Zinc as a Gatekeeper of Immune Function. Nutrients. 2017;9(12):1286. Published 2017 Nov 25. doi:10.3390/nu9121286
[vii] Maares M, Haase H. Zinc and immunity: An essential interrelation. Arch Biochem Biophys. 2016;611:58-65. doi:10.1016/j.abb.2016.03.022
[viii] Wessels I, Maywald M, Rink L. Zinc as a Gatekeeper of Immune Function. Nutrients. 2017;9(12):1286. Published 2017 Nov 25. doi:10.3390/nu9121286
[ix] Maares M, Haase H. Zinc and immunity: An essential interrelation. Arch Biochem Biophys. 2016;611:58-65. doi:10.1016/j.abb.2016.03.022
[x] Wessels I, Maywald M, Rink L. Zinc as a Gatekeeper of Immune Function. Nutrients. 2017;9(12):1286. Published 2017 Nov 25. doi:10.3390/nu9121286
[xi] Shah UH, Abu-Shaheen AK, Malik MA, Alam S, Riaz M, Al-Tannir MA. The efficacy of zinc supplementation in young children with acute lower respiratory infections: a randomized double-blind controlled trial. Clin Nutr. 2013;32(2):193-199. doi:10.1016/j.clnu.2012.08.018
[xii] Hunter J, Arentz S, Goldenberg J, et al. Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2021;11(11):e047474. Published 2021 Nov 2. doi:10.1136/bmjopen-2020-047474
[xiii] Arentz S, Hunter J, Yang G, et al. Zinc for the prevention and treatment of SARS-CoV-2 and other acute viral respiratory infections: a rapid review. Adv Integr Med. 2020;7(4):252-260. doi:10.1016/j.aimed.2020.07.009
[xiv] Razzaque MS. COVID-19 pandemic: Can zinc supplementation provide an additional shield against the infection?. Comput Struct Biotechnol J. 2021;19:1371-1378. doi:10.1016/j.csbj.2021.02.015
[xv] Yasui Y, Yasui H, Suzuki K, et al. Analysis of the predictive factors for a critical illness of COVID-19 during treatment － relationship between serum zinc level and critical illness of COVID-19. Int J Infect Dis. 2020;100:230-236. doi:10.1016/j.ijid.2020.09.008
[xvi] Thomas S, Patel D, Bittel B, et al. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial. JAMA Netw Open. 2021;4(2):e210369. doi:10.1001/jamanetworkopen.2021.0369
[xvii] Skrovanek S, DiGuilio K, Bailey R, et al. Zinc and gastrointestinal disease. World J Gastrointest Pathophysiol. 2014;5(4):496-513. doi:10.4291/wjgp.v5.i4.496
[xviii] Mahmood A, FitzGerald AJ, Marchbank T, et al. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut. 2007;56(2):168-175. doi:10.1136/gut.2006.099929
[xix] Semrad CE. Zinc and intestinal function. Curr Gastroenterol Rep. 1999;1(5):398-403. doi:10.1007/s11894-999-0021-7
[xx] Skrovanek S, DiGuilio K, Bailey R, et al. Zinc and gastrointestinal disease. World J Gastrointest Pathophysiol. 2014;5(4):496-513. doi:10.4291/wjgp.v5.i4.496
[xxi] Fischer Walker CL, Black RE. Micronutrients and diarrheal disease. Clin Infect Dis. 2007;45 Suppl 1:S73-S77. doi:10.1086/518152
[xxii] Sturniolo GC, Montino MC, Rossetto L, et al. Inhibition of gastric acid secretion reduces zinc absorption in man. J Am Coll Nutr. 1991;10(4):372-375. doi:10.1080/07315724.1991.10718165
[xxiii] Salama SM, Gwaram NS, AlRashdi AS, et al. A Zinc Morpholine Complex Prevents HCl/Ethanol-Induced Gastric Ulcers in a Rat Model. Sci Rep. 2016;6:29646. Published 2016 Jul 27. doi:10.1038/srep29646
[xxiv] Takeda A. Movement of zinc and its functional significance in the brain. Brain Res Brain Res Rev. 2000;34(3):137-148. doi:10.1016/s0165-0173(00)00044-8
[xxv] S. Salimi, M. Kianpoor, M.R. Abassi, M. Abdani and E.S. Moghaddam, 2008. Lower Total Serum Protein, Albumin and Zinc in Depression in an Iranian Population. Journal of Medical Sciences, 8: 587-590.
[xxvi] Takeda A. Movement of zinc and its functional significance in the brain. Brain Res Brain Res Rev. 2000;34(3):137-148. doi:10.1016/s0165-0173(00)00044-8
[xxvii] Szewczyk B, Szopa A, Serefko A, Poleszak E, Nowak G. The role of magnesium and zinc in depression: similarities and differences. Magnes Res. 2018;31(3):78-89. doi:10.1684/mrh.2018.0442
[xxviii] Petrilli MA, Kranz TM, Kleinhaus K, et al. The Emerging Role for Zinc in Depression and Psychosis. Front Pharmacol. 2017;8:414. Published 2017 Jun 30. doi:10.3389/fphar.2017.00414
[xxix] Dwivedi Y. Brain-derived neurotrophic factor: role in depression and suicide. Neuropsychiatr Dis Treat. 2009;5:433-449. doi:10.2147/ndt.s5700
[xxx] Petrilli MA, Kranz TM, Kleinhaus K, et al. The Emerging Role for Zinc in Depression and Psychosis. Front Pharmacol. 2017;8:414. Published 2017 Jun 30. doi:10.3389/fphar.2017.00414
[xxxi] Sleiman SF, Henry J, Al-Haddad R, et al. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate. Elife. 2016;5:e15092. Published 2016 Jun 2. doi:10.7554/eLife.15092
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